Pre-print: Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation, 2022, Brew et al

Discussion in 'Long Covid research' started by SNT Gatchaman, Jun 18, 2022.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Aussie breakthrough on the long Covid condition that leaves sufferers with symptoms similar to 'traumatic brain injury (Daily Mail - no really)

    (Kynurenine)


    ETA: Dr Bruce Brew recently co-authored Recent advances in clinical trials targeting the kynurenine pathway (Pires et al, 2021)
     
    Last edited: Jun 18, 2022
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  2. Art Vandelay

    Art Vandelay Senior Member (Voting Rights)

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    @SNT Gatchaman beat me to it!

    No mention of ME/CFS at all, which is a huge oversight given that they're investigating cognitive problems following a viral infection. This sort of ignorance is typical for the Australian medical profession when it comes to post-viral illness.

    Link to pre-print:
    Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study
     
  3. Midnattsol

    Midnattsol Moderator Staff Member

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    Full title of study: Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study

    Abstract
    Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12-months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly (p<.001) declined. Cognitive impairment was more common in those with anosmia (p=.05), but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly (p<.001) associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment.
     
  4. Midnattsol

    Midnattsol Moderator Staff Member

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  5. Hutan

    Hutan Moderator Staff Member

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    I'm only part of the way through the methodology, but this is looking like a solid study.

    People have been followed longitudinally (3, 5, 9 and 13 months) and the study is ongoing (the Sydney St. Vincent’s Hospital COVID-19 ADAPT prospective study). The people had to have a confirmed Covid-19 infection. It should be noted that the study isn't specifically of people with Long Covid - it's a prospective study and includes 128 people covering mild, moderate and hospitalised patients. I guess I have the question of, 'is the study big enough to pick up enough people developing ME/CFS?'

    They have assessed a lot of things and checked for relationships between them. They seem to have taken good approaches and are transparent about what they did and about things like dropouts (which weren't high). It almost sounds as though the world might have it's act together - there's mention of the International Neuropsychology COVID-19 taskforce's recommendations for cognitive studies "where consideration of disease severity, demographics, mental health, objectively tested olfaction, and co-morbidities is conducted a priori."

    Cognitive assessment
    The International Neuropsychology COVID-19 taskforce informed their choice of the CogState Computerized Battery (CCB)
    They've considered issues like practice effects, and the different cognitive performances of different demographics and adjusted cognitive performance data to produce z values (as in, indications for departures from the expected value, given the person's demographic groups). The CCB has normative Australian data that was used in that standardisation process.


    Peripheral biomarkers of brain injury
    neuro-axonal with Neurofilament Light Chain (NFL);
    astrogliosis with Glial fibrillary acidic protein (GFAP);
    blood brain barrier permeability (BBB), brain injury and astrocytosis with S100β;
    macrophage and granulocyte proliferation with Granulocyte macrophage colony-stimulating factor (GMCSF)),
    and because each is abnormally elevated in COVID-19 infection (NFL28; GFAP29; S100β30; GMCSF31).


    A range of blood cytokines and components of the kynurenine pathway
    (Interferons (IFNs), major Interleukins, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α),
    Evaluation of recovery

    Evaluation of mental health

    I thought the 'Depression in the Medically Ill' questionnaire sounded interesting

    Inter-relationships between measures
     
    Last edited: Jun 19, 2022
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  6. Hutan

    Hutan Moderator Staff Member

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    This finding of a trend to increasing prevalence of clinically significant cognitive impairment over time (with quite a big increase from 16% to 26%) I think probably isn't important. It's not statistically significant. Although there weren't a lot of dropouts, perhaps the less cognitively disabled were less likely to be motivated to keep coming along to the study assessments. Perhaps there was something a bit off with their adjustments to the data for practice effects.


    That's quite an important finding, although it sounds as though some of the authors weren't very happy with it. It seems that they had expected to find something different, and they are recommending more studies to find that 'something different'.

     
  7. Hutan

    Hutan Moderator Staff Member

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    Seems that loss of smell and cognitive dysfunction aren't associated.

    And cognitive dysfunction wasn't associated with illness severity or lung function.
     
    Last edited: Jun 19, 2022
  8. Hutan

    Hutan Moderator Staff Member

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    Finally to the most interesting bit, but I'm running out of steam. All those cytokines and brain injury markers and yet all they report finding that was abnormal related to the kynurenine pathway.


    If it was just the KP data, we might assume that this is just related to the acute illness, with the effects wearing off over time. But, the fact that there was an association with cognitive dysfunction makes it a lot more interesting for us.

    I'm going to sign off for the night, but it would be interesting to poke around in the KP data.

    I do hope Long Covid and ME/CFS researchers will eventually stop doing studies on broad swathes of peripheral blood cytokines. There must be enough literature around now to suggest that the answer isn't going to be found there.
     
  9. Hutan

    Hutan Moderator Staff Member

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    Gilles Guillemin is listed as the second to last author. Brew and Guillemin were both co-authors of that other recent KP paper mentioned in the first post of this thread.
     
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  10. rvallee

    rvallee Senior Member (Voting Rights)

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    Uh, would you look at that, someone who can think about things rationally. Can't remember having seen this in the many years looking at research for mental illness in the physically ill.

    The choice of instruments, even poor ones, is a matter of judgment. There is no science that gives the right answer, it's a conscious choice. Very telling that this is never used in BPSland. Even when they do the thing where they pretend like it's legitimate to argue of a "functional overlay" when disease may explain illness, just not to their satisfaction.

    Obviously this questionnaire would give opposite results to what BPS ideologues seek out. That's why they keep inventing more BS questionnaires that give them the answers they want.
     
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  11. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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  12. Ravn

    Ravn Senior Member (Voting Rights)

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    The DMI with instructions, scoring etc can be downloaded here:
    https://www.blackdoginstitute.org.au/education-services/health-professionals/psychological-toolkit/

    The 10 questions are:
    1. Are you stewing over things?
    2. Do you feel more vulnerable than usual?
    3. Are you being self-critical and hard on yourself?
    4. Are you feeling guilty about things in your life?
    5. Do you find that nothing seems to be able to cheer you up?
    6. Do you feel as if you have lost your core and essence?
    7. Are you feeling depressed?
    8. Do you feel less worthwhile?
    9. Do you feel hopeless or helpless?
    10. Do you feel more distant from other people?
    Certainly less bad than some we've seen but still plenty of potential for misinterpretation for pwME (and, I suspect, other conditions, too). Q10 for example. Some pwME could easily feel more distant from other people because they really are more distant. Just being physically unable to see other people in person creates distance, both real and felt. Whether a person is depressed or not because of that distance is a separate question.

    For diagnostic purposes, I really don't understand why they can't just ask Q7 and be done with it. Why would an ambiguous questionnaire be better at identifying depression than the person themselves?

    The other questions could be useful as follow-up if a person said that yes they are depressed, to drill deeper into the problem and work out the best way to help. Discussing, not just tick-boxing, the questions could help identify what aspects are genuine depression and what aspects are more practical problems caused by their medical illness (e.g. someone might feel depressed and helpless because they live alone and can't cope with the cooking and cleaning, in which case home help would be a better prescription than pills). Using the questions that way would make sense but that's different from diagnostic use.
     
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  13. rvallee

    rvallee Senior Member (Voting Rights)

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    Ugh. Nevermind, awful. Not sure why I expected otherwise.

    In hindsight, medicine being more accepting of mental illness may have been the worst thing to happen to mental health. What a mess of things they made.

    Although the fact that it was mostly accepted because of how easy it is to abuse the concept and kick people out of medical care may have been a bit of a tell about where things would go. And that it was largely driven by psychiatrists working with insurance companies. And many other giant red flags.
     
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  14. LarsSG

    LarsSG Senior Member (Voting Rights)

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    The very brief PHQ-2 might be best for depression in ME (or Long Covid, etc) and is already well known:

    Over the last 2 weeks, how often have you been bothered by the following problems?
    1.Little interest or pleasure in doing things
    2.Feeling down, depressed or hopeless

    Though even question 1 could arguably measure ME symptoms rather than depression, depending how people read it. Much better than the PHQ-9 in any case.
     
  15. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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